Association between serum ferritin and mortality : findings from the USA, Japan and European Dialysis Outcomes and Practice Patterns Study

Background: The Kidney Disease: Improving Global Outcomes guidelines have cautioned against administering intravenous (IV) iron to hemodialysis patients with high serum ferritin levels due to safety concerns, but prior research has shown that the association between high ferritin and mortality could be attributed to confounding by malnutrition and inflammation. Our goal was to better understand the ferritin-mortality association and relative influence of IV iron and inflammation in the USA, where ferritin levels have recently increased dramatically, and in Europe and Japan, where ferritin levels are lower and anemia management practices differ. Methods: Data from 18 261 patients in Phases 4 and 5 (2009-15) of the international Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, were analyzed. Using Cox regression, we modeled the association between baseline ferritin and 1-year mortality with restricted cubic splines and assessed the impact of potential confounders. Results: Median ferritin levels were 718 ng/mL in the USA, 405 in Europe and 83 in Japan. High ferritin levels were associated with elevated mortality (relative to region-specific medians) in all three regions. The strength of this association was attenuated more by adjustment for malnutrition and inflammation than by IV iron and erythropoiesis-stimulating agent dose in each region. Conclusion: The utility of high ferritin as a biomarker for clinical risk due to excess iron stores may be limited, although caution regarding IV iron dosing to higher upper ferritin targets remains warranted. Research to resolve biomarker criteria for iron dosing, and whether optimal anemia management strategies differ internationally, is still needed

Cosmic distance-duality as probe of exotic physics and acceleration

In cosmology, distances based on standard candles (e.g. supernovae) and standard rulers (e.g. baryon oscillations) agree as long as three conditions are met: (1) photon number is conserved, (2) gravity is described by a metric theory with (3) photons travelling on unique null geodesics. This is the content of distance-duality (the reciprocity relation) which can be violated by exotic physics. Here we analyse the implications of the latest cosmological data sets for distance-duality. While broadly in agreement and confirming acceleration we find a 2-sigma violation caused by excess brightening of SN-Ia at z > 0.5, perhaps due to lensing magnification bias. This brightening has been interpreted as evidence for a late-time transition in the dark energy but because it is not seen in the d_A data we argue against such an interpretation. Our results do, however, rule out significant SN-Ia evolution and extinction: the "replenishing" grey-dust model with no cosmic acceleration is excluded at more than 4-sigma despite this being the best-fit to SN-Ia data alone, thereby illustrating the power of distance-duality even with current data sets.Comment: 6 pages, 4 colour figures. Version accepted as a Rapid Communication in PR

A Burgessian critique of nominalistic tendencies in contemporary mathematics and its historiography

We analyze the developments in mathematical rigor from the viewpoint of a Burgessian critique of nominalistic reconstructions. We apply such a critique to the reconstruction of infinitesimal analysis accomplished through the efforts of Cantor, Dedekind, and Weierstrass; to the reconstruction of Cauchy's foundational work associated with the work of Boyer and Grabiner; and to Bishop's constructivist reconstruction of classical analysis. We examine the effects of a nominalist disposition on historiography, teaching, and research.Comment: 57 pages; 3 figures. Corrected misprint

Mortality risk in patients on hemodiafiltration versus hemodialysis : a 'real-world' comparison from the DOPPS

Background. With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes. Methods. In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume. Results. Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF > 20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities usingmore HDF (versus HD). Conclusions. Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices

Advances in the Projective Dynamics Method: A Procedure of Discretizing the Space applied to Markovian Processes

AbstractThe projection of a continuous space process to a discrete space process via the transition rates between neighboring bins allows us to relate a master equation to a solution of a stochastic differential equation. The presented method is formulated in its general form for the first time and tested with the Brownian Diffusion process of noninteracting particles with white noise in simple one-dimensional potentials. The comparison of the first passage time obtained with Projective Dynamics, Brownian motion simulations and analytical solutions show the accuracy of this method as well as a wide independence of the particular choice of the binning process

From error bounds to the complexity of first-order descent methods for convex functions

This paper shows that error bounds can be used as effective tools for deriving complexity results for first-order descent methods in convex minimization. In a first stage, this objective led us to revisit the interplay between error bounds and the Kurdyka-\L ojasiewicz (KL) inequality. One can show the equivalence between the two concepts for convex functions having a moderately flat profile near the set of minimizers (as those of functions with H\"olderian growth). A counterexample shows that the equivalence is no longer true for extremely flat functions. This fact reveals the relevance of an approach based on KL inequality. In a second stage, we show how KL inequalities can in turn be employed to compute new complexity bounds for a wealth of descent methods for convex problems. Our approach is completely original and makes use of a one-dimensional worst-case proximal sequence in the spirit of the famous majorant method of Kantorovich. Our result applies to a very simple abstract scheme that covers a wide class of descent methods. As a byproduct of our study, we also provide new results for the globalization of KL inequalities in the convex framework. Our main results inaugurate a simple methodology: derive an error bound, compute the desingularizing function whenever possible, identify essential constants in the descent method and finally compute the complexity using the one-dimensional worst case proximal sequence. Our method is illustrated through projection methods for feasibility problems, and through the famous iterative shrinkage thresholding algorithm (ISTA), for which we show that the complexity bound is of the form $O(q^{k})$ where the constituents of the bound only depend on error bound constants obtained for an arbitrary least squares objective with $\ell^1$ regularization

Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?

Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by 'buzzing' (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance, allowing genes for disease susceptibility to persist in plant populations. We speculate that enhanced pollinator service for infected individuals in wild plant populations might provide mutual benefits to the virus and its susceptible hosts.Major funding for this project was provided to JPC by the Leverhulme Trust (Grant numbers RPG-2012-667 and F/09741/F: https://www. leverhulme.ac.uk/). Additional funding to JPC and studentships to support JHW and SCG came from the Biotechnological and Biological Sciences Research Council (Grant number BB/J011762/1: http://www.bbsrc.ac.uk/). Other additional funding was obtained from the Isaac Newton Trust (http://www. newtontrust.cam.ac.uk/: grant number 12.07/I to AMM).This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/:10.1371/journal.ppat.100579

Quantum Optics and Photonics

Contains reports on nine research projects.U.S. Air Force - Office of Scientific Research (Contract F49620-82-C-0091)U.S. Air Force - Rome Air Development CenterJoint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation Grant (Grant PHY 82-710369